Lithium may seem like a scary drug. It can cause severe side effects and be toxic to different organs of the body. But toxicity usually happens only with high doses, while lithium is probably still the single most effective psychiatric drug. Is fear really warranted? Read on to learn about the signs and symptoms of lithium toxicity and how it is treated.

What is Lithium Toxicity?

Lithium toxicity (also known as lithium overdose or lithium poisoning) develops when the amount of lithium in your body becomes too high. This usually happens when you take too much lithium [1].

Lithium is known as a mood stabilizer and is commonly used in psychiatric conditions, like bipolar disorder and depression [1].

In fact, it’s the first psychiatric drug. Lithium was first used for mania in the 1940s – long before modern antidepressants. Some even argue that it unfairly fell out of favor precisely because newer, more expensive drugs were being marketed by companies [1, 2].

Even today, some doctors consider lithium the single most effective treatment in psychiatry. Its side effects are easy to manage. Many people stay on low-dose lithium for decades. But overdoses still occur, especially with high doses and in people who have been prescribed several medications [2].

According to some estimates, about 1 in 100 patients experience moderate to severe lithium toxicity each year. Toxicity occurs more frequently in women and the elderly [3].

So even if you’ve been prescribed high-dose lithium, there’s a small chance you’ll experience severe side effects and overdose. But you should know what overdose looks like, because it often requires immediate medical treatment [3].

The toxic effects of lithium generally become worse as the level of lithium in the blood increases. Symptoms of toxicity can range from nausea and vomiting in mild cases to brain damage and even death in cases of severe intoxication [3].

Luckily, less than 1% of lithium toxicity cases result in death as long as proper medical treatment is received [4, 5].

People who take lithium for a long time may also experience negative effects on certain organs, like the kidneys as well as the thyroid and parathyroid glands [1, 6].

Different Types of Toxicity

Lithium toxicity can be divided into 3 categories [7].

Acute toxicity occurs when someone who hasn’t taken lithium before suddenly takes a high dose. This can happen when a person accidentally takes a prescription lithium pill or when someone purposely takes a lot of lithium for self-harm [3].

Chronic toxicity appears in those who regularly take lithium medications at too high of a dose, leading to constantly elevated lithium levels [3].

Acute-on-chronic toxicity can be the most dangerous form. This happens when a person who is currently taking lithium takes even more lithium than normal, either accidentally or intentionally [3].

Lithium toxicity is also sometimes classified based on severity.

Mild toxicity typically refers to lithium blood levels between 1.5 and 2.5 mmol/L [7].

Moderate toxicity occurs at lithium blood levels between 2.5 and 3.5 mmol/L [7].

Severe toxicity occurs at lithium blood levels greater than 3.5 mmol/L [7].

However, these definitions are not universal – ranges may vary depending on who you ask [3].

Causes of Lithium Toxicity

Lithium Medication (Prescription)

The main cause of lithium toxicity is prescription lithium medications.

This can happen in a number of ways. Maybe you accidentally took an extra lithium pill. Or perhaps your dose is too high, leading to elevated lithium levels. Either way, even small increases in your blood levels can cause toxicity [8].

This is because lithium has a narrow therapeutic window, which means its blood concentration needs to be in a tight range for it to be effective and safe [8].

A doctor will typically try to keep your lithium levels somewhere between 0.5 to 1.2 mmol/L. Levels above this range may lead to more side effects and toxicity, while levels below this may make the drug ineffective [8].

In general, signs of toxicity start to appear at lithium levels above 1.5 mmol/L [9, 10].

Lithium levels should not go above 2.0 mmol/L, which can lead to serious toxicity [9, 10].

However, toxicity can occur at any lithium level, even at normal or therapeutic levels. Therefore, each person’s target range may be somewhat different. The elderly are especially susceptible to toxicity at lower levels [1, 11].

Drug Interactions

Certain drugs can interact with prescription lithium and make toxicity more likely. This doesn’t necessarily mean you can’t take lithium with these drugs, only that close monitoring by your doctor is required [12].

According to some estimates, up to 85% of bipolar patients use two or more medications at once, including lithium [13].

Another study found that about 12% of lithium toxicity cases are associated with drug interactions [3].

Medications that can increase lithium blood levels include [12]:

  • Thiazide diuretics (hydrochlorothiazide) ~20 to 40% increase
  • Loop diuretics (furosemide) ~0 to 40% increase
  • ACE inhibitors (lisinopril, benazepril) ~20 to 40% increase
  • ARBs (losartan, valsartan) ~0 to 20% increase
  • NSAIDs (aspirin, ibuprofen) ~0 to 40% increase

There are also various case reports of other drug interactions, including tetracycline, methyldopa, phenytoin, haloperidol, and lactulose [14, 15, 16, 17, 18].

Let your doctor know about all the medications and supplements you are taking to avoid possible interactions.

What About Other Lithium Sources?

Prescription lithium drugs are not the only source of lithium available.

Lithium supplements, mainly in the form of lithium orotate, can be purchased over the counter by anyone. Lithium is also found in much of the food and water we consume [19].

Many mineral springs contain lithium. Some of them, such as Mineral Wells in Texas, have long-held reputations as “crazy waters.” Texas was well known for its mineral water resorts back in the 19th century. Thousands of “crazy” people and those with various chronic health problems used to gush to these springs to get the healing benefits of lithium [2]

This begs the question: Can this lithium from water, food, and low-dose supplements also cause toxicity?

Supplements

Let’s take a look at supplements first.

Lithium orotate (a popular lithium supplement) commonly contains about 4 mg of actual or elemental lithium per 100 mg dose [19].

This is in contrast to lithium carbonate (the prescription form of lithium), which contains about 19 mg of lithium per 100 mg [19].

Also, keep in mind their dosage differences:

  • Lithium carbonate is typically prescribed at doses of 900-1800 mg/day. This would give you about 170-340 mg of elemental lithium.
  • Lithium orotate usually contains only 5 mg of elemental lithium per dose.

This means that, at normal doses, prescription lithium drugs are over 30x stronger than lithium orotate, making toxicity from supplements very unlikely.

However, there are still a few case reports of intoxication from lithium supplements [20, 21].

In one case, a woman experienced nausea and vomiting after ingesting 18 tablets of lithium orotate. Despite taking such an excessive amount, her lithium levels peaked at 0.4 mmol/L, a far cry from levels normally associated with toxicity (> 1.5 mmol/L) [20].

Food and Water

The amount of lithium in food and drinking water is even lower than supplements.

Even foods that are considered lithium-rich have minuscule amounts of lithium compared to prescription medications [19].

For example, nuts (one of the most lithium-rich foods) only have 8.8 micrograms of lithium per gram [19].

As mentioned, some mineral waters are quite high in lithium – like those famous “crazy waters” in Texas. We already spoke about lithium deficiency where we deal with lithium food and water sources – check out that article for more details.

The amount of lithium in supplements and food is tiny compared to prescription lithium medications. It is highly unlikely they will ever cause lithium toxicity.

Signs and Symptoms of Lithium Toxicity

Common Signs & Symptoms

The most common signs and symptoms of lithium toxicity (defined as blood levels > 1.5 mmol/L) include [3]:

  • Confusion and disorientation
  • Impaired balance and falling
  • Vomiting and/or diarrhea
  • Agitation
  • Tiredness
  • Tremors
  • Twitching
  • Muscle stiffness and weakness
  • Blurred vision
  • Slurred speech

Confusion and disorientation are the most common symptoms for any kind of lithium toxicity [3].

According to a 17-year-long study of over 1.3k patients, chronic intoxication (high lithium levels over a long period of time) is associated with more neurological symptoms, like tremors and balance issues [3].

On the other hand, acute intoxication (a single ingestion of a high dose of lithium) leads to more mental changes, such as confusion, agitation, and tiredness [3].

Extremely high levels of lithium (> 2.5 mmol/L) can lead to seizures, coma, and even death [22].

Women and the elderly are much more likely to experience symptoms of lithium toxicity [3, 23].

Kidney Damage

Lithium is known to be toxic to certain organs, including the kidneys. This is why people taking lithium medications usually need to monitor their kidney function [8].

Lithium reduces the rate at which blood is filtered by the kidneys [1].

It also reduces the urine concentrating ability of the kidneys by as much as 15% [1].

These factors can eventually lead to kidney failure, but research suggests the risk is fairly low (only 0.5% according to some estimates) [1].

Generally, the benefits of lithium will outweigh the risks of kidney injury. Even in those with kidney disease, lithium may be continued with careful monitoring [6, 8].

Thyroid and Parathyroid Damage

Regular thyroid level checks are also important if you’re taking lithium. Thyroid and parathyroid problems occur in about 25% of patients on lithium [1].

Lithium has several negative effects on the thyroid gland, including blocking T4 and iodine uptake. This can increase TSH levels and eventually lead to hypothyroidism [24, 1].

Lithium also blocks the calcium-sensing receptor in the parathyroid gland, which impairs its function. This leads to an increase in calcium and parathyroid hormone in the blood, which can develop into hyperparathyroidism [1].

In Pregnancy

Lithium use during pregnancy can be a complicated issue.

Lithium is known to have toxic effects on the fetus. More specifically, it may cause certain types of heart defects. Women with bipolar disorder also have a higher risk of pregnancy complications [25, 26].

But stopping lithium is sometimes not a viable option, especially for women experiencing severe bipolar symptoms [8].

The decision to stop or continue lithium during pregnancy requires a doctor to carefully weigh the benefits and risks [8].

If lithium is continued, monitoring the baby’s heart is usually recommended [8].

Breastfeeding while taking lithium is typically not recommended, but that is also up to a doctor’s discretion [8].

Lithium Toxicity Treatment

Anyone who shows symptoms of lithium toxicity should seek immediate medical attention.

Treatment depends on several factors, including the severity of symptoms and the lithium level in the blood. Hospitals may also have differing protocols for handling intoxication [27, 7].

Moderate or severe toxicity usually requires time in the intensive care unit [7].

Treatment of lithium toxicity may include [3]:

  • IV hydration
  • Activated charcoal
  • Gastric lavage (stomach pumping)
  • Whole bowel irrigation
  • Dialysis

In mild cases, a doctor may simply stop the lithium medication and monitor the patient’s progress [4].

When properly treated, lithium toxicity rarely leads to death. Some studies indicate that less than 1% of lithium toxicity cases are fatal [4, 5].

Patients will typically stay in the hospital until all toxicity symptoms are gone and their lithium blood level drops below 1.5 mmol/L [27, 7].

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Takeaway

Common signs and symptoms of lithium toxicity include confusion, disorientation, impaired balance, vomiting and/or diarrhea. Long-term use of lithium may also cause injury to the kidneys, thyroid, and parathyroid glands. Extremely high lithium levels can lead to coma and even death.

However, lithium is not as dangerous as it may seem. Just because you’re taking prescription lithium in no way means you’ll experience toxicity. Your doctor should monitor your blood levels to prevent this, while common side effects are mild and easy to manage.

If you or someone you know may be experiencing lithium toxicity, get medical help right away.

About the Author

Mathew Eng, PharmD

PharmD

Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.

Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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